In an attempt to characterize the nature of the receptors on cell surfaces and of the viral protein involved in this initial interaction between rotavirus and cells, several approaches have been followed. (1) Enzymatic treatment of human type O erythrocytes before utilization in hemagglutination assay has resulted in the separation of rhesus and bovine (NCDV strain) rotaviruses into one group and two avian rotavirus isolates into another group with respect to their ability to agglutinate these enzymatically treated erythrocytes. (2) Non-hemagglutinating human rotaviruses have been shown to bind to human erythrocytes in a modified radioimmunoassay using the erythrocytes as solid phase. (3) Labeled rotavirus has been shown to react with membrane proteins isolated from both the microvillus of enterocytes of the small intestine of pigs as well as from human erythrocytes. (4) Rotavirus was demonstrated to bind to glycosphigolipids in a thin layer chromatography system. (5) The viral protein involved in the initial binding to MA 104 cells has in preliminary experiments been found to have a molecular weight of approximately 20,000 daltons.